953 resultados para low-density lipoprotein receptor-related protein


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In this study, a novel kind of hybrid pigment based on nanoclays and dyes was synthesized and characterized. These nanoclay-based pigments (NCPs) were prepared at the laboratory with sodium montmorillonite nanoclay (NC) and methylene blue (MB). The cation-exchange capacity of NC exchanged with MB was varied to obtain a wide color gamut. The synthesized nanopigments were thoroughly characterized. The NCPs were melt-mixed with linear low-density polyethylene (PE) with an internal mixer. Furthermore, samples with conventional colorants were prepared in the same way. Then, the properties (mechanical, thermal, and colorimetric) of the mixtures were assessed. The PE–NCP samples developed better color properties than those containing conventional colorants and used as references, and their other properties were maintained or improved, even at lower contents of dye compared to that with the conventional colorants.

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Plant survival under environmental stress requires the integration of multiple signaling pathways into a coordinated response, but the molecular mechanisms underlying this integration are poorly understood. Stress-derived energy deprivation activates the Snf1-related protein kinases1 (SnRK1s), triggering a vast transcriptional and metabolic reprogramming that restores homeostasis and promotes tolerance to adverse conditions. Here, we show that two clade A type 2C protein phosphatases (PP2Cs), established repressors of the abscisic acid (ABA) hormonal pathway, interact with the SnRK1 catalytic subunit causing its dephosphorylation and inactivation. Accordingly, SnRK1 repression is abrogated in double and quadruple pp2c knockout mutants, provoking, similarly to SnRK1 overexpression, sugar hypersensitivity during early seedling development. Reporter gene assays and SnRK1 target gene expression analyses further demonstrate that PP2C inhibition by ABA results in SnRK1 activation, promoting SnRK1 signaling during stress and once the energy deficit subsides. Consistent with this, SnRK1 and ABA induce largely overlapping transcriptional responses. Hence, the PP2C hub allows the coordinated activation of ABA and energy signaling, strengthening the stress response through the cooperation of two key and complementary pathways.

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Oggigiorno la ricerca di nuovi materiali per gradatori di campo da impiegarsi in accessori di cavi ha iniziato a studiare alcuni materiali nano dielettrici con proprietà elettriche non lineari con la tensione ed aventi proprietà migliorate rispetto al materiale base. Per questo motivo in questo elaborato si sono studiati materiali nanostrutturati a base di polietilene a bassa densità (LDPE) contenenti nano polveri di grafene funzionalizzato (G*), ossido di grafene (GO) e carbon black (CB). Il primo obiettivo è stato quello di selezionare e ottimizzare i metodi di fabbricazione dei provini. La procedura di produzione è suddivisa in due parti. Nella prima parte è stata utilizzatala tecnica del ball-milling, mentre nella seconda un pressa termica (thermal pressing). Mediante la spettroscopia dielettrica a banda larga (BDS) si sono misurate le componenti reali e immaginarie della permettività e il modulo della conducibilità del materiale, in tensione alternata. Il miglioramento delle proprietà rispetto al provino di base composto dal solo polietilene si sono ottenute quando il quantitativo delle nanopolveri era maggiore. Le misure sono state effettuate sia a 3 V che a 1 kV. Attraverso misurazioni di termogravimetria (TGA) si è osservato l’aumento della resistenza termica di tutti i provini, soprattutto nel caso quando la % di nanopolveri è maggiore. Per i provini LDPE + 0.3 wt% GO e LDPE + 0.3 wt% G* si è misurata la resistenza alle scariche parziali attraverso la valutazione dell’erosione superficiale dei provini. Per il provino contenente G* è stato registrato una diminuzione del 22% del volume eroso, rispetto al materiale base, mentre per quello contenente GO non vi sono state variazioni significative. Infine si è ricercata la resistenza al breakdown di questi ultimi tre provini sopra citati. Per la caratterizzazione si è fatto uso della distribuzione di Weibull. Lo scale parameter α risulta aumentare solo per il provino LDPE + 0.3 wt% G*.

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Transportation Department, Office of Research and Development Policy, Washington, D.C.

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Ohio Department of Transportation, Columbus

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"May 1976."

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"The experimental study reported here has been performed under the sponsorship of the Fluid Dynamics Branch, Aeronautical Research laboratories of the U.S. Air Force Air Research and Development Command, Contract no. AF 33(616)-6025."

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Recently very potent extracorporeal cholesterol-lowering treatment options have become available for patients with hypercholesterolemia. LDL immunoapheresis treatment selectively removes LDL and lipoprotein(a) from the circulation. Since LDL is the major carrier of lipophilic antioxidants in plasma, the purpose of the present study was to assess the effects of a single LDL apheresis treatment on plasma concentrations of tocopherols (alpha- and gamma-tocopherol) and carotenoids (alpha- and beta-carotene, zeaxanthin, cryptoxanthin, canthaxanthin, lycopene, and retinol). Plasma antioxidant concentrations were determined by HPLC in 7 patients with familial hypercholesterolemia before and after LDL immunoapheresis treatment. Plasma concentrations of both alpha- and gamma-tocopherol and the different carotenoids were significantly reduced by LDL apheresis. However, when standardized for cholesterol to adjust for cholesterol removal, alpha- and gamma-tocopherol, retinol, and the more polar carotenoids lutein and zeaxanthin increased in response to apheresis treatment, while the more unpolar carotenoids such as beta-carotene and lycopene did not change. These data demonstrate that a single LDL immunoapheresis treatment affects tocopherols and individual carotenoids differently. This may be explained by differences in chemical structure and preferential association with different lipoproteins. These results further imply that tocopherols, lutein, zeaxanthin, and retinol, are associated in part with lipoproteins and other carriers such as retinol-binding protein that are not removed during apheresis treatment. (C) 2004 Wiley-Liss, Inc.

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Urban encroachment on dense, coastal koala populations has ensured that their management has received increasing government and public attention. The recently developed National Koala Conservation Strategy calls for maintenance of viable populations in the wild. Yet the success of this, and other, conservation initiatives is hampered by lack of reliable and generally accepted national and regional population estimates. In this paper we address this problem in a potentially large, but poorly studied, regional population in the State that is likely to have the largest wild populations. We draw on findings from previous reports in this series and apply the faecal standing-crop method (FSCM) to derive a regional estimate of more than 59 000 individuals. Validation trials in riverine communities showed that estimates of animal density obtained from the FSCM and direct observation were in close agreement. Bootstrapping and Monte Carlo simulations were used to obtain variance estimates for our population estimates in different vegetation associations across the region. The most favoured habitat was riverine vegetation, which covered only 0.9% of the region but supported 45% of the koalas. We also estimated that between 1969 and 1995 similar to 30% of the native vegetation associations that are considered as potential koala habitat were cleared, leading to a decline of perhaps 10% in koala numbers. Management of this large regional population has significant implications for the national conservation of the species: the continued viability of this population is critically dependent on the retention and management of riverine and residual vegetation communities, and future vegetation-management guidelines should be cognisant of the potential impacts of clearing even small areas of critical habitat. We also highlight eight management implications.

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HepG2 cells were stably transfected with human caveolin-1 (HepG2/cav cells). Transfection resulted in expression of caveolin-1 mRNA, a high abundance of caveolin-1 protein, and the formation of caveolae on the plasma membrane. Cholesterol efflux from HepG2/cav cells was 280 and 45% higher than that from parent HepG2 cells when human plasma and human apoA-I, respectively, were used as acceptors. The difference in efflux was eliminated by treatment of cells with progesterone. There was no difference in cholesterol efflux to cyclodextrin. Cholesterol efflux from plasma membrane vesicles was similar for the two cell types. Transfection led to a 40% increase in the amount of plasma membrane cholesterol in cholesterol-rich domains ( caveolae and/or rafts) and a 67% increase in the rate of cholesterol trafficking from intracellular compartments to these domains. Cholesterol biosynthesis in HepG2/cav cells was increased by 2-fold, and cholesterol esterification was reduced by 50% compared with parent HepG2 cells. The proliferation rate of transfected cells was significantly lower than that of non-transfected cells. Transfection did not affect expression of ABCA1 or the abundance of ABCA1 protein, but decreased secretion of apoA-I. We conclude that overexpression of caveolin-1 in hepatic cells stimulates cholesterol efflux by enhancing transfer of cholesterol to cholesterol-rich domains in the plasma membrane.

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The Wilms' tumour suppressor gene, WT1, encodes a zinc-finger protein that is mutated in Wilms' tumours and other malignancies. WT1 is one of the earliest genes expressed during kidney development. WT1 proteins can activate and repress putative target genes in vitro, although the in vivo relevance of such target genes often remains unverified. To better understand the role of WT1 in tumorigenesis and kidney development, we need to identify downstream target genes. In this study, we have expression pro. led human embryonic kidney 293 cells stably transfected to allow inducible WT1 expression and mouse mesonephric M15 cells transfected with a WT1 antisense construct to abolish endogenous expression of all WT1 isoforms to identify WT1-responsive genes. The complementary overlap between the two cell lines revealed a pronounced repression of genes involved in cholesterol biosynthesis by WT1. This pathway is transcriptionally regulated by the sterol responsive element-binding proteins (SREBPs). Here, we provide evidence that the C-terminal end of the WT1 protein can directly interact with SREBP, suggesting that WT1 may modify the transcriptional function of SREBPs via a direct protein-protein interaction. Therefore, the tumour suppressor activities of WT1 may be achieved by repressing the mevalonate pathway, thereby controlling cellular proliferation and promoting terminal differentiation.

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The Rho family GTPases are regulatory molecules that link surface receptors to organisation of the actin cytoskeleton and play major roles in fundamental cellular processes. In the vasculature Rho signalling pathways are intimately involved in the regulation of endothelial barrier function, inflammation and transendothelial leukocyte migration, platelet activation, thrombosis and oxidative stress, as well as smooth muscle contraction, migration, proliferation and differentiation, and are thus implicated in many of the changes associated with atherogenesis. Indeed, it is believed that many of the beneficial, non-lipid lowering effects of statins occur as a result of their ability to inhibit Rho protein activation. Conversely, the Rho proteins can have beneficial effects on the vasculature, including the promotion of endothelial repair and the maintenance of SMC differentiation. Further identification of the mechanisms by which these proteins and their effectors act in the vasculature should lead to therapies that specifically target only the adverse effects of Rho signalling. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

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Endothelial cell apoptosis contributes to atherosclerosis and may be exacerbated by oxidative stress. Results from clinical trials using antioxidant supplementation are equivocal and could be enhanced by antioxidants with additional non-antioxidant properties such as a-lipoic acid and alpha-tocopherol. The aim of this study was to investigate the effects of these antioxidants on cytoprotective pathways and endothelial apoptosis. Endothelial cells were incubated with alpha-lipoic acid and alpha-tocopherol, alone or in combination, prior to incubation with H2O2 or staurosporine. alpha-lipoic acid pre-treatment alone increased caspase-3 activity in a dose-dependent manner. Both H2O2 and staurosporine increased DNA fragmentation and caspase-3 activity and pre-treatment of cells with a-lipoic acid and/or a-tocopherol failed to prevent stress-induced apoptosis. Neither antioxidant treatments nor apoptotic inducers alone altered expressions of BcI-2, Bax, HSP70 or pERK1/2 or pJNK. alpha-lipoic decreased pERK2 in staurosporine-treated cells in a dose-dependent manner. These findings indicate that pre-incubation with alpha-lipoic acid and alpha-tocopherol, alone or in combination, does not protect against oxidative- or non-oxidative-induced apoptosis in endothelial cells. Moreover, we have demonstrated a non-antioxidant, dose-dependent role of alpha-lipoic acid in caspase-3 and ERK2 activation. These data provide an insight and indicate caution in the use of high doses of alpha-lipoic acid as an antioxidant.

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Although low-density lipoprotein (LDL)-cholesterol lowering with the statins reduces the mortality and morbidity associated with coronary artery disease, considerable mortality and morbidity remains. Berberine upregulates the LDL receptor (LDLR) by a mechanism distinct from that of the statins, which involves stabilising the LDLR mRNA. In hamsters fed a high-fat and high-cholesterol diet for 2 weeks, the oral administration of berberine 100 mg/kg for 10 days reduced total serum cholesterol from ∼ 4.8 to 2.7 mmol/l, and LDL-cholesterol from ∼ 2.5 to 1.4 mmol/l. In subjects with hypercholesterolaemia, berberine hydrochloride (0.5 g b.i.d. for 3 months) reduced LDL-cholesterol (from 3.2 to 2.4 mmol/l) without any effect on high-density lipoprotein-cholesterol. Berberine also caused a reduction in triglyceride levels from 2.3 to 1.5 mmol/l. As berberine and statins both upregulate LDLR, their lipid-lowering profiles are similar. Thus, this mechanism is unlikely to make berberine an attractive alternative to statins for lipid lowering in most circumstances. However, the other effects of berberine (anti hypertensive, inotropic and class III antiarrhythmic properties) may make it a useful agent in the treatment of cardiovascular disease.

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Many insect parasitoids that deposit their eggs inside immature stages of other insect species inactivate the cellular host defence to protect the growing embryo from encapsulation. Suppression of encapsulation by polydnavirus-encoded immune-suppressors correlates with specific alterations in hemocytes, mainly cytoskeletal rearrangements and actin-cytoskeleton breakdown. We have previously shown that the Cotesia rubecula polydnavirus gene product CrV1 causes immune suppression when injected into the host hemocoel. CrV1 is taken up by hemocytes although no receptors have been found to bind the protein. Instead CrV1 uptake depends on dimer formation, which is required for interacting with lipophorin, suggesting a CrV1-lipophorin complex internalisation by hemocytes. Since treatment of hemocytes with oligomeric lectins and cytochalasin D can mimic the effects of CrV1, we propose that some dimeric and oligomeric adhesion molecules are able to cross-link receptors on the cell surface and depolymerise actin by leverage-mediated clearance reactions in the hemolymph.